Abstract
9552 Purpose: To test whether insulin-like growth factor-1 (IGF-1) ameliorates or prevents radiation-induced kidney dysfunction and to establish the dose-effect relationship for this growth factor which has not previously been studied in conjunction with kidney irradiation. Background: The kidney is one of the most radiosensitive organs in the abdomen. Therefore, modification of its radiation response might improve the therapeutic ratio in the treatment of retroperitoneal tumors as well as gastric and other malignancies. Material and Methods: Adult female C3H mice were treated with single-fraction radiotherapy to the right kidney with doses of 10–17 Gy ± IGF-1. The kidney function was assessed prior to radiotherapy, 19 weeks thereafter and then every 6 weeks by means of 99mTc-DMSA scans, i.e. static scintigraphy. Maximum follow-up was 12 months. IGF-1 was given subcutaneously either concomitant to radiotherapy or after deterioration of the kidney function, i.e. after 5–6 months. At least 5 mice per group received concomitant IGF-1 starting 24h before irradiation for 3 days or 2 weeks. Delayed treatment after deterioration of the kidney function was administered over 4 weeks, immediately followed by repeat scans every 6 weeks. Doses of IGF-1 were 0.5–25 μg per injection. Results: The function of the irradiated kidney continuously declined during follow-up in all control groups in a dose-dependent fashion. Concomitant treatment with IGF-1 significantly reduced the number of mice with a severe decline, defined as loss of function of 50% or more. In contrast to controls, no statistically significant decline of the mean kidney function was observed in the best IGF-1 group. The best dose of IGF-1 was 5 μg per injection, administered over 2 weeks. Delayed treatment after deterioration of the kidney function was unable to restore the function regardless of the IGF-1 dose. Very few animals with delayed IGF-1 showed at least stabilisation of the compromised function. Conclusion: IGF-1 showed activity as a radioprotective agent when given concomitant to high-dose kidney irradiation. The optimum dose of IGF-1 was 5 μg per injection. In contrast, established renal insufficiency did not improve after IGF-1 treatment. No significant financial relationships to disclose.
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